A. Field Of The Invention
The present invention is directed to a method for determining the correct dilution of a calibrator solution, any calibrator solution, such as provided in a test kit, particularly a diagnostic test kit. More particularly, the present invention is directed to a method for conveniently determining the quantity or concentration of a calibrator in a solution that has been diluted from a stock solution of calibrator. The present invention is useful because it provides a convenient method by which a manufacturer of a calibrator solution can confirm the correct dilution of any calibrator solution that is made from an original stock solution. The present invention is especially useful where the calibrator material is an antigen or an antibody.
B. Background
Test kits for the analysis of a chemical or biochemical analyte are often provided with one or more solutions containing different concentrations of the analyte that are used to generate a calibration curve, i.e., "calibrator solutions." In these calibrator solutions, the analyte, or occasionally a chemically similar material (i.e., an analog), is used as the calibration material. During the commercial manufacturing of a solution containing a calibrator, the manufacturer often prepares a concentrated solution containing a predetermined amount of calibrator ("the stock solution"). The concentration of the calibrator material in this stock solution is precisely analyzed. Thereafter, and as needed, the manufacturer would prepare a diluted solution of the calibrator (i.e., a "working solution"), such as provided in a test kit, by diluting a precise aliquot of the stock solution to a precise volume. In many test kits, the manufacturer is required to prepare a series of calibrator solutions that encompass the working range of the test kit for the analyte of interest.
It is insufficient for any manufacturer of calibrator solutions to assume that all dilutions were made correctly from an original stock solution. The calibrator solutions must be subject to a quality control process to confirm that the dilutions of the stock solution to produce a working series of calibrator solutions were performed correctly. This is particularly true where the calibrator solution(s) is (are) part of a diagnostic test kit that provides the user with information upon which medical or veterinary decisions are made.
In many diagnostic test kits, the analyte is a complex antigenic molecule. To assure correspondence between the analyte and the calibrator material, the analyte is preferably the same as the calibrator material in the calibrator solutions. Conventional quality control ("Q.C.") and quality assurance ("Q.A.") analysis by a kit manufacturer for such analytes in a calibrator solution is complex, requires expensive reagents, and occasionally requires a long time (i.e., up to three days). Many diagnostic test kits, particularly those that provide a quantitative result, have up to six solutions that span a range of calibrator concentrations. In these multi-calibrator kits, the conventional analysis of the calibrator solutions by the kit's manufacturer is very costly and labor intensive. It is also an object of the present invention to provide a quick, simple, and reliable method that allows a kit manufacturer to confirm that a stock solution of a complex calibrator material, such as a ligand or antiligand, was diluted correctly during the manufacturing of working solutions of the calibrator. It is a further object of the present invention to provide a method for Q.C. or Q.A. by a kit manufacturer that neither requires a complex antigen antibody reaction nor multiple reaction sequences.
Currently, there are a variety of commercially available test kits. Each kit measures its respective analyte of interest using any one of a variety of signal-producing systems. These signal-producing systems include colorimetric, fluorimetric, phosphorescent, radiolabeling, chemiluminescent and the like. Accordingly, it is a further object of the present invention to provide a method for confirmation of the dilution of the stock calibrator solution that is accurate yet does not interfere with the signal used to measure the presence or concentration of the analyte.
Most manufacturers of calibrator solutions also manufacture "control solutions." Like calibrator solutions, control solutions are also prepared by precise dilution of a known amount of a stock solution that contains the control material. Whether a solution is a calibrator solution or a control solution is generally a matter of designation by the manufacturer. Accordingly, it is a further object of the present invention to provide a method that allows a kit or component manufacturer to confirm that a stock solution containing a control material was diluted accurately.
The ultimate user of a diagnostic test kit that contains calibration and/or control solutions is a diagnostic laboratory. The medical technologist in such a laboratory is often faced with the task of performing a number of diagnostic test procedures concurrently. One of the critical parts of any diagnostic test procedure is the maintenance of correct specimen identification. Prior to the pipetting step, the calibrator solutions, control solutions and patient samples are lined up in a precise sequence that gets logged in. Because one calibration solution looks like another, there is the possibility that the technologist, under the stress of performing multiple tasks, may transpose the alignment of one or more calibrator and/or control solutions. Further, a solution may inadvertently be mispipetted altogether. Once the calibrator and/or control solutions have been pipetted into an individual test tube, the chance of detecting and timely correcting the error before running the assay becomes even more remote. Many diagnostic assays have multiple steps and require from hours to days to complete before an error in transposition or pipetting would be detected.
Accordingly, it is an object of the present invention to also provide a method whereby a technologist or user of a diagnostic test kit would, in a timely fashion, detect and correct a pipetting error or transposition prior to a complete running of the diagnostic assay.